An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8℃), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission. Keywords: DRESS syndrome; Allopurinol; Jaundice
Feasibility and Efficacy of Stereotactic Ablative Radiotherapy for Barcelona Clinic Liver Cancer-C Stage Hepatocellular CarcinomaThe purpose of this study was to assess the feasibility and efficacy of stereotactic ablative radiotherapy (SABR) for liver tumor in patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC).We retrospectively reviewed the medical records of 35 patients between 2003 and 2011.Vascular invasion was diagnosed in 32 patients, extrahepatic metastases in 11 and both in 8. Thirty-two patients were categorized under Child-Pugh (CP) class A and 3 patients with CP class B. The median SABR dose was 45 Gy (range, 30-60 Gy) in 3-5 fractions.The median survival time was 14 months.The 1-and 3-yr overall survival (OS) rate was 52% and 21%, respectively.On univariate analysis, CP class A and biologically equivalent dose ≥ 80 Gy10 were significant determinants of better OS.Severe toxicity above grade 3, requiring prompt therapeutic intervention, was observed in 5 patients.In conclusion, SABR for BCLC-C stage HCC showed 1-yr OS rate of 52% but treatment related toxicity was moderate.We suggest that patients with CP class A are the best candidate and at least SABR dose of 80 Gy10 is required for BCLC-C stage.
Objectives The relationship between HCV genotype and the development of more serious liver disease has not been clearly established. This study was to investigate the distribution pattern of HCV genotypes in Korea and their relationship to the viremic level and to progression of chronic liver disease. Methods Study population was 217 patients with type C chronic liver disease. They were divided into 4 groups: 83 patients with near-normal ALT (group 1), 64 patients with elevated ALT (group 2), 20 patients with decompensated liver cirrhosis (group 3) and 50 patients with hepatocellular carcinoma (group 4). HCV genotypes were determined by reverse transcription polymerase chain reaction (RT-PCR) using mixed primer sets, and then the fidelity of genotyping was confirmed by cloning and sequencing. HCV RNA concentration was measured by quantitative competitive RT-PCR for 23 patients in group 2. Results The genotypes could be determined in 166 (76%) out of 217 patients. Type 1b and type 2a were predominantly occurring over the other types in somewhat similar frequency (45% and 51%, respectively). The genotype distribution of type 1b and 2a among four different groups showed 42% and 54% in group 1, 49% and 45% in group 2, 53% and 47% in group 3 and 41% and 57% in group 4; thus there was no significant difference in genotype distribution among 4 different disease groups. However, the viremia levels in patients with genotype 1b infection were significantly higher than those with genotype 2a. Conclusion Genotype 2a infection is as prevalent as genotype 1b in Korea, and genotype 2a infection may pose no less risk for progression of disease despite lower replication level than genotype 1b infection.
A deficiency in bone morphogenetic protein receptor type 2 (BMPR2) signaling is a central contributor in the pathogenesis of pulmonary arterial hypertension (PAH). We have recently shown that endothelial-specific Bmpr2 deletion by a novel L1Cre line resulted in pulmonary hypertension. SMAD1 is one of the canonical signal transducers of the BMPR2 pathway, and its reduced activity has been shown to be associated with PAH. To determine whether SMAD1 is an important downstream mediator of BMPR2 signaling in the pathogenesis of PAH, we analyzed pulmonary hypertension phenotypes in Smad1 -conditional knockout mice by deleting the Smad1 gene either in endothelial cells or in smooth muscle cells using L1Cre or Tagln -Cre mouse lines, respectively. A significant number of the L1Cre(+); Smad1 (14/35) and Tagln -Cre(+); Smad1 (4/33) mutant mice showed elevated pulmonary pressure, right ventricular hypertrophy, and a thickening of pulmonary arterioles. A pulmonary endothelial cell line in which the Bmpr2 gene deletion can be induced by 4-hydroxy tamoxifen was established. SMAD1 phosphorylation in Bmpr2 -deficient cells was markedly reduced by BMP4 but unaffected by BMP7. The sensitivity of SMAD2 phosphorylation by transforming growth factor-β1 was enhanced in the Bmpr2 -deficient cells, and the inhibitory effect of transforming growth factor-β1–mediated SMAD2 phosphorylation by BMP4 was impaired in the Bmpr2 -deficient cells. Furthermore, transcript levels of several known transforming growth factor-β downstream genes implicated in pulmonary hypertension were elevated in the Bmpr2 -deficient cells. Taken together, these data suggest that SMAD1 is a critical mediator of BMPR2 signaling pertinent to PAH, and that an impaired balance between BMP4 and transforming growth factor-β1 may account for the pathogenesis of PAH.
Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways.
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